Prostate cancer will become an epidemic male health problem due to increasing life expectancy. There is a critical need for accurate imaging evaluation of patients with metastatic prostate cancer. Positron emission tomography (PET) with the most common tracer currently available, [F-18]-fluorodeoxyglucose (FDG), has emerged as an important diagnostic imaging modality in cancer. Recent advances in imaging technology have also resulted in dual-modality PET-CT systems that allow precise fusion of anatomic and metabolic imaging data. Our preliminary in-vitro cell culture, animal in-vivo, and pilot clinical studies have provided compelling evidence that FDG PET may have a significant role in the imaging evaluation of patients with metastatic prostate cancer. There are two specific aims for this research proposal: 1) to assess the diagnostic utility of FDG PET-CT in the evaluation of therapy response in two clinically distinct groups of patients with metastatic prostate cancer, Group I: men with newly diagnosed hormone-naive metastatic disease who will be treated with the standard androgen ablation therapy, and Group II: men with newly developed hormone-refractory metastatic cancer who will be treated with standard chemotherapy, and 2) to evaluate FDG PET-CT in predicting patient outcome. We hypothesize that semi-quantitative FDG PET-CT monitoring of the serial changes in the glucose metabolism of metastatic prostate cancer lesions provides a competitive advantage over the conventional methods in the objective assessment of treatment response and in predicting key clinical outcomes. To test this hypothesis, we will perform a prospective cohort study to evaluate the diagnostic and prognostic utility of serial FDG PET-CT imaging in determining tumor metabolic response to either androgen ablation therapy or to chemotherapy and in predicting key clinical outcomes such as time to hormone-refractory state and survival. Rigorous statistical methods will be applied to determine the diagnostic and prognostic performance of FDG PET-CT in this clinical setting.